Parp12, a mon(ADP-ribosyl) transferase of the poly(ADP-ribosyl) polymerase (PARP) family, is involved in multiple biological processes. It participates in protein translation, and its associated pathways include those related to DNA repair, gene expression, RNA processing, and ribosome biogenesis. Poly(ADP-ribosyl)ation (PARylation), of which Parp12-mediated Mono(ADP-ribosyl)ation (MARylation) is a part, is crucial in many physiological functions [1].

Gene knockout studies have been instrumental in revealing Parp12's functions. In mouse oocytes, Parp12 depletion leads to abnormal spindle organization, chromosome misalignment, increased aneuploidy frequency, activation of the spindle assembly checkpoint, and attenuated F-actin, disrupting oocyte meiotic maturation [1]. In thermogenic adipocytes, knockdown of Parp12 reduces UCP1 expression and mitochondrial respiration, indicating its importance in maintaining mitochondrial function [2]. In a study on coronavirus, Parp12 -/- mice showed increased replication of a Mac1 mutant coronavirus in bone-marrow-derived macrophages and mice, demonstrating its role in repressing virus replication [3,4]. In hepatocellular carcinoma, Parp12 deficiency promotes cell migration, invasion, and metastasis by regulating the epithelial-mesenchymal transition process through interaction with FHL2 [5].

In summary, Parp12 is essential for oocyte meiotic maturation, mitochondrial function in thermogenic adipocytes, antiviral response against certain coronaviruses, and acts as a tumor suppressor in hepatocellular carcinoma. Gene knockout mouse models have been vital in uncovering these functions, providing insights into the role of Parp12 in these biological processes and disease conditions.